13 February, 2017
25,000 genes
200 immunity genes
6 class I HLA genes
1958 HLA I gene identified
About 12,000 idenitified to date
DNA, RNA and protein
Possibility, potential and actual | Alleles and allotypes
1986 Alain Townsend
What HLA proteins are showing the immune system
1987 Pamela Bjorkman
The structure of the HLA protein
Peptide length distribution
Peptides are catergorical, from 20 amino acid alphabet e.g. LLFGYPVYV
Recap
- There are thousands of these HLA genes
- We each have up to 6 HLA genes expressing HLA proteins
- HLA proteins present peptides
- 100 x 103 HLA molecules per cell
- 10 x 103 unique peptides per cell
- Peptides are coded in a 20 letter amino acid alphabet
- Peptide length ranges mostly 8-15 amino acids. 9-mers dominate.
- And that's how T-cells know what is going inside cells
How do chemicals cause allergic responses?
Aim
Characterise the peptidomes of skin cells \(\pm\)DNCB to identify allergenic peptides
Technical and cost limitations
- 1,000 GBP per replicate
- 4-6 weeks per replicate
- Recovery is 1-3% of total peptides.
Replication: Bassani-Sternberg et al. 2015
Replication: Bassani-Sternberg et al. 2015
Quantifying uncertainty
- What is the likelihood that the peptides seen under our two conditions arise from different underlying populations?
Or to put it another way:
- What is the probability of seeing peptide X, given condition \(+\)DNCB, versus the probability of seeing peptide X in given condition \(-\)DNCB?